GREFIXYL 10 MG/ML + 2 MG/ML EYE DROPS, SUSPENSION

2. What you need to know before you start using Grefixyl

Do not use Grefixyl

• if you are allergic to brinzolamide or brimonidine tartrate or any of the other ingredients of this medicine (listed in section 6).
• if you are allergic to sulfonamides (including, for example, medicines used to treat diabetes and infections, and also diuretics (water pills)).
• if you are taking monoamine oxidase inhibitors (MAOIs) (including, for example, medicines to treat depression or Parkinson's disease) or certain antidepressants. You should inform your doctor if you are taking any medicine for depression.
• if you have severe kidney problems.
• if you have too much acid in the blood (a disease called hyperchloremic acidosis).
• in newborns and children under 2 years of age.

Warnings and Precautions

Consult your doctor, ophthalmologist (eye specialist) or pharmacist before starting to use this medicine if you currently have or have had in the past:

• liver problems.
• a type of high pressure in the eyes called narrow-angle glaucoma.
• dry eyes or corneal problems.
• heart disease (symptoms may include pressure or pain in the chest, shortness of breath or choking), heart failure, low or high blood pressure.
• depression.
• circulatory disorders (such as Raynaud's disease, Raynaud's syndrome, or cerebral insufficiency).
• if you have ever developed a severe skin rash or skin peeling or blisters and/or sores in the mouth after using Grefixyl or other related medicines.

Be careful with Grefixyl:

Severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported in association with brinzolamide treatment. Stop using Grefixyl and seek immediate medical attention if you notice any symptoms related to these severe skin reactions described in section 4.

If you wear soft contact lenses, do not use this eye drop with the contact lenses in place. See below under the section "If you wear contact lenses - Grefixyl contains benzalkonium chloride".

Children and Adolescents

Grefixyl is not indicated for use in children and adolescents under 18 years of age because it has not been studied in this age group. It is especially important that this medicine is not used in children under 2 years of age (see previous section "Do not use Grefixyl") because it is unlikely to be safe.

Other Medicines and Grefixyl

Tell your doctor, ophthalmologist (eye specialist) or pharmacist if you are using, have recently used, or might use any other medicines.

Grefixyl may affect or be affected by other medicines you are using, including other eye drops for the treatment of glaucoma.

Consult your doctor if you are using or plan to use any of the following medicines:

• medicines to lower blood pressure.
• heart medicines, including digoxin (used to treat heart conditions).
• other glaucoma medicines that are also used to treat high altitude sickness, known as acetazolamide, methazolamide, and dorzolamide.
• medicines that may affect metabolism, such as chlorpromazine, methylphenidate, and reserpine.
• antiviral, antiretroviral (used to treat Human Immunodeficiency Virus (HIV)) or antibiotic medicines.
• antifungal (medicines against fungal infections) or antilevuric (medicines against yeast infections) medicines.
• monoamine oxidase inhibitors (MAOIs) or antidepressants, including amitriptyline, nortriptyline, clomipramine, mianserin, venlafaxine, and duloxetine.
• anesthetics.
• sedatives, opioids, or barbiturates.

You should also inform your doctor if the dose of any of your current medicines changes.

Using Grefixyl with Alcohol

If you regularly drink alcohol, consult your doctor, ophthalmologist (eye specialist), or pharmacist before using this medicine. Grefixyl may be affected by alcohol.

Pregnancy and Breastfeeding

If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor, ophthalmologist (eye specialist), or pharmacist before using this medicine. It is recommended that women who may become pregnant use effective contraceptive methods during treatment with Grefixyl. The use of Grefixyl is not recommended during pregnancy. Do not use Grefixyl unless clearly indicated by your doctor.

If you are breastfeeding, Grefixyl may pass into breast milk. The use of Grefixyl is not recommended during breastfeeding.

Driving and Using Machines

Immediately after applying Grefixyl, you may notice that your vision becomes blurry or abnormal. Grefixyl may also cause dizziness, drowsiness, or fatigue in some patients.

Do not drive or use machines until the symptoms have disappeared.

If you wear contact lenses - Grefixyl contains benzalkonium chloride

This medicine contains 0.15 mg of benzalkonium chloride per 5 ml, which is equivalent to 0.03 mg/ml.

Benzalkonium chloride can be absorbed by soft contact lenses and may alter the color of the contact lenses. Remove the contact lenses before using this medicine and wait 15 minutes before putting them back. Benzalkonium chloride may cause eye irritation, especially if you have dry eyes or other corneal diseases (the transparent layer of the front of the eye). Consult your doctor if you feel any strange sensation, itching, or pain in the eye after using this medicine.

3. How to use Grefixyl

Follow the instructions for administration of this medicine exactly as indicated by your doctor, ophthalmologist (eye specialist), or pharmacist. If you are unsure, consult your doctor, ophthalmologist (eye specialist), or pharmacist again.

Use Grefixyl only in your eyes. Do not swallow or inject.

The recommended doseis one drop in the affected eye(s) twice a day. Use it at the same time every day.

How to use

• Wash your hands before starting.

• Shake well before use.
• Remove the cap from the bottle. After removing the cap, the security seal ring must be removed before using this medicine.
• Do not touch the dropper with your fingers when opening or closing the bottle, as the drops may become contaminated.
• Hold the bottle, upside down, between your thumb and index finger. Tilt your head back.
• Gently pull down the lower eyelid of the eye to form a pouch, where the drop should fall (figure 1).
• Bring the tip of the bottle close to the eye. You can use a mirror to help you.
• Do not touch the eye, eyelid, or surrounding areas with the dropper, as the drops may become contaminated.
• Gently press the base of the bottle to release one drop of Grefixyl.

Do not squeeze the bottle: it is designed so that gentle pressure on the base is enough (figure 2).

After using this eye drop, close your eyes and press the edge of the eye, next to the nose, for at least 2 minutes. This helps prevent the medicine from passing into the rest of the body.

If you apply drops to both eyes, repeat the above steps for the other eye. It is not necessary to close and shake the bottle between administrations of both eyes. Tighten the cap well after using the product.

If you are using other eye drops as well as Grefixyl, wait at least 5 minutes between the application of Grefixyl and the other drops.

If a drop falls outside the eye, try again.

If you use more Grefixyl than you should

You can rinse it off with lukewarm water. Do not apply more drops until it is time for the next dose.

Adults who accidentally ingested medicines containing brimonidine experienced a decrease in heart rate, a decrease in blood pressure that may be followed by an increase in blood pressure, heart failure, difficulty breathing, and effects on the nervous system. If this happens, contact your doctor immediately.

Severe side effects were reported in children who had accidentally ingested medicines containing brimonidine. The signs included drowsiness, weakness, low body temperature, paleness, and difficulty breathing. If this happens, contact your doctor immediately.

If you have accidentally ingested Grefixyl, contact your doctor immediately.

If you forget to use Grefixyl

Continue with the next scheduled dose. Do not apply a double dose to make up for forgotten doses. Do not apply more than one drop twice a day in the affected eye(s).

If you stop using Grefixyl

Do not stop using Grefixyl without consulting your doctor first, as the pressure in your eye may not be controlled, which could lead to vision loss.

If you have any further questions about the use of this medicine, ask your doctor, ophthalmologist (eye specialist), or pharmacist.

4. Possible Side Effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If you experience any of the following side effects, stop using this medicine and seek immediate medical attention, as they may be signs of a reaction to the medicine. The frequency of an allergic reaction to this medicine is not known (cannot be estimated from the available data).

• Severe skin reactions, including rash or redness or itching in the eyes or body.
• Breathing problems.
• Chest pain, irregular heartbeat.

Contact your doctor immediately if you feel dizzy or extremely tired.

The following side effects have been observed with Grefixyl and with other medicines that contain brinzolamide or brimonidine separately.

Stop using Grefixyl and seek immediate medical attention if you notice any of the following symptoms:

• red, target-like, or circular patches on the trunk, often with central blisters, skin peeling, ulcers in the mouth, throat, nose, genitals, and eyes. These severe skin rashes may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis).

Common(may affect up to 1 in 10 people)

• Eye effects: allergic conjunctivitis (allergy in the eye), inflammation of the eye surface, eye pain, eye discomfort, blurred or abnormal vision, eye redness.
• Other side effects: drowsiness, dizziness, bad taste, dry mouth.

Uncommon(may affect up to 1 in 100 people)

• Eye effects: damage to the eye surface with cell loss, eyelid inflammation, deposits on the eye surface, sensitivity to light, eye swelling (affecting the cornea or eyelid), dry eye, eye discharge, watery eyes, eyelid redness, abnormal or decreased sensation in the eyes, tired eyes, reduced vision, double vision, product particles in the eyes.
• Other side effects: low blood pressure, chest pain, irregular heartbeat, slow or fast heart rate, palpitations, difficulty sleeping (insomnia), nightmares, depression, general weakness, headache, dizziness, nervousness, irritability, feeling unwell, memory loss, shortness of breath, asthma, nosebleeds, cold symptoms, nasal or throat dryness, sore throat, throat irritation, cough, nasal discharge (runny nose), stuffy nose, sneezing, sinusitis, chest congestion, ringing in the ears, indigestion, intestinal gas or abdominal pain, nausea, diarrhea, vomiting, abnormal sensation in the mouth, increased allergy symptoms on the skin, rash, abnormal sensation on the skin, hair loss, generalized itching, increased blood chloride levels, or decreased red blood cell count in blood tests, pain, back pain, muscle pain or spasms, kidney pain that appears as lower back pain, decreased sexual desire, sexual problems in men.

Rare(may affect up to 1 in 10,000 people)

• Eye effects: decreased pupil size.
• Other side effects: fainting, increased blood pressure.

Frequency Not Known(cannot be estimated from the available data)

• Eye effects: decreased eyelash growth.
• Other side effects: tremors, decreased sensation, loss of taste, abnormal liver function test values observed in blood tests, facial swelling, joint pain, frequent urination, chest pain, swelling of the limbs, red, target-like, or circular patches on the trunk, often with central blisters, skin peeling, ulcers in the mouth, throat, nose, genitals, and eyes that may be preceded by fever and flu-like symptoms. These severe skin rashes can be potentially life-threatening (Stevens-Johnson syndrome, toxic epidermal necrolysis).

Reporting Side Effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this package leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storing Grefixyl

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the bottle and carton after "EXP". The expiry date is the last day of the month stated.

This medicine does not require any special storage conditions.

To avoid infections, discard the bottle 4 weeks after the first opening. Write the opening date on the space provided on the carton.

Medicines should not be disposed of via wastewater or household waste. Place the packaging and any unused medicines in the SIGRE collection point at your pharmacy. Ask your pharmacist how to dispose of the packaging and any unused medicines. This will help protect the environment.

6. Container contents and additional information

Grefixyl composition

• The active ingredients are brinzolamide and brimonidine tartrate.One ml of suspension contains 10 mg of brinzolamide and 2 mg of brimonidine tartrate, equivalent to 1.3 mg of brimonidine.
• The other components are benzalkonium chloride (50% solution) (see section 2 "If you wear contact lenses - Grefixyl contains benzalkonium chloride"), propylene glycol (E1520), carbomer 974P, boric acid (E284), sodium chloride, tiloxapol, sodium hydroxide and/or hydrochloric acid (to adjust pH) and water for injectable preparations.

Very small amounts of sodium hydroxide and/or hydrochloric acid are added to maintain normal acidity levels (pH levels).

Product appearance and container contents

White LDPE bottle of 10 ml with an LDPE dropper tip and a white HDPE/LDPE cap with a tamper-evident seal, containing 5 ml of a homogeneous white to off-white suspension.

The following pack sizes are available: boxes containing 1 x 5 ml and 3 x 5 ml.

Only some pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

Laboratory STADA, S.L. Frederic Mompou, 5

08960 Sant Just Desvern (Barcelona)

Spain

Manufacturer

Balkanpharma-Razgrad AD

68 Aprilsko vastanie Blvd.

7200 Razgrad

Bulgaria

or

Pharmathen S.A.

Dervenakion 6

15351 Pallini, Athens

Greece

or

STADA Arzneimittel AG

Stadastrasse 2 – 18

61118 Bad Vilbel

Germany

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

DE: Grefixyl 10 mg/ml + 2 mg/ml Augentropfensuspension

ES: Grefixyl 10 mg/ml + 2 mg/ml eye drops suspension

Date of last revision of this leaflet: October 2023

Detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS)

http://www.aemps.gob.es/